Tirzepatide is associated with a higher incidence of gastrointestinal adverse events, including nausea (25.1% vs. 22.4%), vomiting (11.6% vs. 9.7%), and diarrhea (24.8% vs. 19.1%), compared to dulaglutide in adults with type 2 diabetes and atherosclerotic cardiovascular disease, though rates of severe events and discontinuation remain low.

Tirzepatide activates two receptors in the gut and brain that slow down how fast food moves through the stomach and intestines. This makes the stomach feel fuller longer and triggers signals that cause nausea, vomiting, and loose stools. Dulaglutide only activates one of these receptors, so it doesn’t slow digestion as much, which is why these side effects happen more often with tirzepatide.